Impaired type I interferon regulation in the blood transcriptome of recurrent asthma exacerbations.

ABSTRACT: BACKGROUND:Asthma exacerbations are an important cause of morbidity in asthma. Respiratory infections are often involved in asthma exacerbations in both children and adults. Some individuals with asthma have increased susceptibility to viral infections and as a result increased rates of asthma exacerbations. We sought to identify a transcriptomic signature in the blood associated with asthma exacerbations triggered by respiratory infections (AETRI) and determine its association with increased risk for asthma exacerbations. METHODS:We conducted a two-step study using publicly available, previously generated transcriptomic signatures in peripheral blood mononuclear cells (PBMCs) from asthmatics to identify novel markers of increased risk for asthma exacerbations. In the 1st step, we identified an in vitro PBMC signature in response to rhinovirus. In the 2nd step, we used the in vitro signature to filter PBMC transcripts in response to asthma exacerbations in an independent in vivo cohort. Three different subgroups were identified and studied in the in vivo cohort: 1. Single AETRI; 2. Multiple AETRIs; and 3. Single non-infectious asthma exacerbations. We performed pathway and network analyses in all independent comparisons. We also performed an immunologic gene set enrichment analysis (GSEA) of the comparison between single AETRI and non-infectious asthma exacerbations. RESULTS:The in vitro signature identified 4354 differentially expressed genes (DEGs) with a fold change (FC) ? 1.2, false discovery rate (FDR)?

SUBMITTER: Gomez JL 

PROVIDER: S-EPMC5830339 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature